Perturbations in dermal blood flow, temperature, and skin color were analyzed using laser-speckle contrast imaging, infrared and polarized-light colorimetry following cold-hand immersion (CHI) challenges in patients with cold-induced urticaria compared to the response in healthy controls. Evidence for mast cell degranulation was established by documentation of serum histamine levels and the localized release of tryptase in post-challenge urticarial biopsies. Laser-speckle contrast imaging quantified the attenuated response to cold challenge in patients on cetirizine. We found that the vascular response provoked by mast cell degranulation is rapid and extensive. At the tissue level, it is characterized by a uniform pattern of increased blood flow, thermal warming, vasodilation, and recruitment of collateral circulation. These vascular responses are modified by the administration of an anti-histamine. Monitoring the hemodynamic responses within tissues that are a consequence of mast cell degranulation provides additional insight into the evolution of the allergic inflammatory response and offers a unique approach to assess the effectiveness of treatment intervention.